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Sexually Dimorphic Gene Expression Associated with Growth and Reproduction of Tongue Sole (Cynoglossus Semilaevis) Revealed by Brain Transcriptome Analysis

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Sexually Dimorphic Gene Expression Associated with Growth and Reproduction of Tongue Sole (Cynoglossus Semilaevis) Revealed by Brain Transcriptome Analysis International Journal of Molecular Sciences Article Sexually Dimorphic Gene Expression Associated with Growth and Reproduction of Tongue Sole (Cynoglossus semilaevis) Revealed by Brain Transcriptome Analysis Pingping Wang 1,†, Min Zheng 1,2,†, Jian Liu 3, Yongzhuang Liu 3, Jianguo Lu 1,* and Xiaowen Sun 1 1 Heilongjiang River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Harbin 150070, China; [email protected] (P.W.); [email protected] (M.Z.); [email protected] (X.S.) 2 Environmental Engineering Program, Department of Civil Engineering, Auburn University, Auburn, AL 36849, USA 3 School of Computer Science and Technology, Harbin Institute of Technology, Harbin 150001, China; [email protected] (J.L.); [email protected] (Y.L.) * Correspondence: [email protected]; Tel.: +86-451-8486-1322 † These authors contributed equally to this work. Academic Editors: Jun Li and Li Lin Received: 25 March 2016; Accepted: 19 August 2016; Published: 26 August 2016 Abstract: In this study, we performed a comprehensive analysis of the transcriptome of one- and two-year-old male and female brains of Cynoglossus semilaevis by high-throughput Illumina sequencing. A total of 77,066 transcripts, corresponding to 21,475 unigenes, were obtained with a N50 value of 4349 bp. Of these unigenes, 33 genes were found to have significant differential expression and potentially associated with growth, from which 18 genes were down-regulated and 12 genes were up-regulated in two-year-old males, most of these genes had no significant differences in expression among one-year-old males and females and two-year-old females. A similar analysis was conducted to look for genes associated with reproduction; 25 genes were identified, among them, five genes were found to be down regulated and 20 genes up regulated in two-year-old males, again, most of the genes had no significant expression differences among the other three. The performance of up regulated genes in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was significantly different between two-year-old males and females. Males had a high gene expression in genetic information processing, while female’s highly expressed genes were mainly enriched on organismal systems. Our work identified a set of sex-biased genes potentially associated with growth and reproduction that might be the candidate factors affecting sexual dimorphism of tongue sole, laying the foundation to understand the complex process of sex determination of this economic valuable species. Keywords: sexually dimorphic; tongue sole; transcriptome analysis 1. Introduction Tongue sole (Cynoglossus semilaevis) is a valuable marine fish in China, which is receiving more attention because of its good taste and nutritional value. However, the species is decreasing in number in the wild despite increasing market demand, which favors more production of the species [1]. Apart from its increasing economic value, it also has an intriguing reproductive biology. Genetically, tongue sole has ZW sex-determination system [2]. Males are the homogametic sex (ZZ), while females are the heterogametic sex (ZW). Male and female tongue sole are considerably different in size and Int. J. Mol. Sci. 2016, 17, 1402; doi:10.3390/ijms17091402 www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2016, 17, 1402 2 of 17 growth rate: mature females are twice larger in length and six times greater in weight than their male counterparts [3]. Thus, understanding the underpinning of sexual dimorphism and sex determination in this species is essential for developing methods to boost its productivity to meet the aquaculture market demands. Although sexual determination in some fish is partly determined by the environment [4–6], brain is still a major organ involved in fish growth and reproduction [7], and plays a key role in sexual dimorphism and sex determination, including the regulation of reproduction, maturation and sexual behavior in both sexes. The influence of brain on development is mainly mediated by the Brain–Pituitary–Gonadal (BPG) axis [8]. Gahr [9] found that male quail transplanted with female forebrain do not develop normal testes, indicating that a male brain is necessary for normal testes development. This demonstrates that sexual dimorphism in brain is not entirely determined by hormones secreted by the gonads, and brain develops differently between sexes even before the gonad development [10–12]. Therefore, understanding the mechanism of sexual dimorphism in brain is fundamental for enhancing our knowledge of development processes and exploring the genetic toolkit to maintain or change the difference between sexes. Yang and colleagues [13] found that relatively small changes in gene expression might control functional sexual dimorphism in the brain, suggesting that differences in a few of those genes may become biological significant when interact with other genes in functional gene networks. Thus, uncovering the sex-biased genes are thought to be necessary when studying the mechanism of sexual dimorphism, and these genes may evolve differently under selection pressure, in turn, acting on the sexual phenotype [14]. For researchers, the major challenge is to explain the huge list of differentially expressed genes (DEGs) under certain conditions. A decade ago, automatic functional classification method using Gene Ontology (GO) was proposed to help study the function of these DEGs [15]. The first step is to group the list of DEGs into functional groups, which can offer insight into the biological mechanisms at the given condition. In addition, a well-characterized transcriptome is considered to be helpful to identify functional genes underlying the certain phenotypic variation in several ways. Gonads, as the main sex organ, are often utilized to get a comprehensive overview of differentially expressed genes responsible for sexual dimorphism. Up to now, thousands of sex-biased genes have been identified from gonads in many species, including fruit fly [16], mouse [17] and some teleost, such as zebrafish [18], Nile tilapia [19], sharpsnout seabream [20], guppy [21], and yellow catfish [22]. However, sex-biased genes expressed in brain have been less well studied. For the sexually dimorphic development of tongue sole, studies have mainly focused on the hormones expressed in brain known to influence the BPG-axis such as pituitary adenylate cyclase-activating polypeptide (PACAP) [23,24], growth hormone-releasing hormone (GHRH) [23,24] and growth hormone (GH) [25,26]. However, few studies have been published at the transcriptomic level to identify and characterize sex-biased genes related to growth and reproduction in tongue sole brain. Recently, the whole genome of tongue sole was published [2], enabling whole genome-based transcriptomic analyses. In this study, we seek to identify the molecular mechanism underlying sexual dimorphism of the brain transcriptome of tongue sole. Fish used for this project were one- and two-year-old tongue sole. The average body weights of one-year-old male and female were 54 and 99 g, and the average body lengths were 21 and 25 cm, respectively. For two-year-old fish, the average weights were 337 and 1380 g, and average lengths were 27 and 42 cm, for male and female respectively. Females were much bigger than males. Two-year-old females were still immature, while males were mature. We used the RNA-Sequencing approach [27] aimed at identifying the differentially expressed genes of tongue sole. Brain transcriptomic profiles of one- and two-year-old males and females were analyzed and revealed a number of sexually differentially expressed genes potentially associated with growth and reproduction. These data will hopefully provide a useful genetic resource for further sex determination studies on tongue sole. Int. J. Mol. Sci. 2016, 17, 1402 3 of 17 Int. J. Mol. Sci. 2016, 17, 1402 3 of 17 2. Results Results 2.1. Transcriptome Transcriptome Sequencing and Assembly To obtain comprehensive information of gene expression between sexes, we sequenced four transcriptomes derived derived from from female female and and male male brains brains at at one and two-year-old tongue sole by using Illumina Hiseq2000Hiseq2000 technology. technology. A A workflow workflow with with the transcriptomethe transcriptome data analysisdata analysis procedures procedures is shown is shownin Figure in1 Figure. 1. FigureFigure 1. 1. Work-flowWork-flow of the transcriptome analysis of tongue sole. In total, 201,822,072 paired-end reads were generated, encompassing 20.2 Gb of sequence. Low In total, 201,822,072 paired-end reads were generated, encompassing 20.2 Gb of sequence. quality reads and reads with ambiguous nucleotides were discarded, leaving 191,631,250 clean reads forLow transcriptome quality reads assembly and reads and with analysis. ambiguous To nucleotidesassess our transcriptome were discarded, assembly, leaving 191,631,250we mapped clean our cleanreads paired-end for transcriptome reads to assembly the C. semilaevis and analysis. whole To genome. assess ourApproximately transcriptome 84.2% assembly, of them we exhibited mapped C. semilaevis significantour clean paired-endhits to the readsgenome. to the These reads werewhole assembled genome. into Approximately 77,066 transcripts 84.2% in of themtotal, correspondingexhibited significant to 21,475 hits unigenes, to the genome. with an These averag readse length were of assembled 3059 bp, intothe N50 77,066 value transcripts of 4349 inbp
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